In a pilot study aimed at preparing and testing new liposome types, we have demonstrated that liposomes prepared from cardiolipin and cholesterol, a composition not previously considered, show biodistributions significantly different from that of conventional liposomes. These preliminary results confirm the suggestion that the biodistribution of liposome-born radioactivity is strongly influenced by lipid composition. The object of this proposed research will be to extend this investigation of the effects of lipid composition in order to identify new liposome types with more favorable biodistributions for tumor detection. Specifically, we intend to investigate the effect of surface charge in detail since previous workers have observed that tumor uptake of liposomes is influenced by charge. An important aspect of this study will be the refinement and use of in vitro assay techniques based on ion exchange chromatography to quantitate liposome surface charge and to provide a measure of quality control not always employed in liposome studies. We hope to identify those amphipathic compounds which, in the proper concentration with other lipids, will form liposomes with the desired in vitro and in vivo properties. Compounds such as long chain fatty acids, long chain amines, certain phosphoglycerides, and certain sphingolipids will each be examined in combination with other lipids such as dicetyl phosphate, stearylamine, and cholesterol. In vitro techniques to be employed include light and electron microscopy, gel and ion exchange chromatography, and equilibrium dialysis, in addition to standard counting techniques; in vivo techniques will include biodistribution studies in normal mice and in rat subcutaneous tumor models. The overall object of this work is the development of new types of liposomes which localize more effectively in tumor tissue than those previously considered. The use of these liposomes types will improve the localization of radioactivity in these tissues and thus facilitate tumor detection by imaging and, in addition, may be useful as carriers of therapeutic drugs to these sites.